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. 2013 Jun;7(5-6):316-26.
doi: 10.1002/prca.201300004.

Development of a Label-Free LC-MS/MS Strategy to Approach the Identification of Candidate Protein Biomarkers of Disease Recurrence in Prostate Cancer Patients in a Clinical Trial of Combined Hormone and Radiation Therapy

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Development of a Label-Free LC-MS/MS Strategy to Approach the Identification of Candidate Protein Biomarkers of Disease Recurrence in Prostate Cancer Patients in a Clinical Trial of Combined Hormone and Radiation Therapy

Brian Morrissey et al. Proteomics Clin Appl. .

Abstract

Purpose: Combined hormone and radiation therapy (CHRT) is one of the principle curative regimes for localised prostate cancer (PCa). Following treatment, many patients subsequently experience disease recurrence however; current diagnostics tests fail to predict the onset of disease recurrence. Biomarkers that address this issue would be of significant advantage.

Experimental design: Label-free LC-MS/MS for protein biomarker discovery and MRM for targeted confirmation were applied to patient serum samples accrued in a non-interventional clinical trial of CHRT.

Results: Analysis of time-matched patient samples from a patient with disease recurrence compared with a time match disease-free individual supported the identification of 287 proteins. Of these, 141 proteins were quantified, 95 proteins changed in their expression (P ≤ 0.05 and ≥1.5-fold change) and of these 16 were selected for MRM confirmation. The protein expression changes observed in the label-free LC-MS/MS and MRM analysis were found to be highly correlated (R(2) = 0.85).

Conclusions and clinical relevance: The establishment of a clinical trial to support the acquisition of samples and development of a pipeline for MS-based biomarker discovery and validation should contribute to the identification of a serum protein signature to predict or monitor the outcome of treatment of patients with PCa.

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